The ultimate goal of these studies is to contribute to the understanding of how chemical carcinogens interact with co-carcinogens to yield enhanced cell transformation in vivo, and how the effect of these interactions may be reversed or prevented. The specific aim of this project is to evaluate, at the molecular and cellular levels, the effect of chemical co-carcinogens on the repair of DNA damage induced by various chemical carcinogens. These studies will permit an evaluation of the ability of co-carcinogens to inhibit the repair of the genetic damage induced by a selected number of chemical and physical carcinogenic agents. Concurrently, it will be determined whether modification of DNA repair results in a corresponding change in the frequency of transformation induced by biological, chemical or physical oncogenic agents. A determination of the amount of unrepaired DNA damage of specific physical chemical forms required to produce an oncogenic event will be determined. These comparisons are vital to the working hypothesis that the underlying events leading to malignant transformation involve unrepaired alterations in cellular DNA. For example, it is known that repair of UV-induced pyrimidine dimers is inversely proportional to the frequency of transformation within the teleost Poecilia formosa. BIBLIOGRAPHIC REFERENCES: Hart, R. W. Setlow, R. B., Gibson, R. E. and Hoskins, T. L., DNA Repair--A Possible Control Mechanism for Cellular Aging, Xth International Congress of Gerontology 1, pp. 22-26 (1975). Trosko, J.E. and Hart R. W., DNA Mutation Frequencies in Mammals, Cellular Aspects of Aging, Concepts and Mechanisms, ed. by R. Cutler, S. Karger AG, Basel, Switzerland, 1976.